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Curr Drug Targets. 2017;18(14):1664-1675. doi: 10.2174/1389450118666170104153512.

Pro-Inflammatory Cytokines: New Potential Therapeutic Targets for Obesity-Related Bone Disorders.

Wang T1,2, He C2, Yu X2.

Author information

1
Department of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041. China.
2
Collaborative Innivation Centre of Biotherapy and Cancer Centre, West China Hospital, Sichuan University, No. 37 Guoxue Xiang, Chengdu. China.

Abstract

BACKGROUND:

Obesity was traditionally considered as a positive regulator on the strength of bone. With the in-depth study, obesity is considered as a major risk factor for osteoporosis. Some proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) are the factors that fat uses to negatively regulate bone metabolism.

OBJECTIVE:

This review was aimed to summarize and critically discuss the convincing evidence for the therapeutic effectiveness of pro-inflammatory cytokines for the treatment of obesity-related bone disorders.

RESULTS:

Obese people and animals show a higher level of serum TNF-α and IL-6, which are produced by macrophages derived from adipose tissue. These pro-inflammatory cytokines regulate the proliferation and apoptosis of adipocyte, promote lipolysis, inhibit lipid synthesis and decrease blood lipids through autocrine and paracrine way. On the other hand, TNF-α and IL-6 regulate bone metabolism through the endocrine way. Several reports suggest that TNF-α is a negative regulator of osteoblast at some stages of differentiation and positively regulates osteoclast proliferation and differentiation. In contrast, IL-6 influences osteoblasts and osteoclasts through complex mechanisms, which reflect dual effects. In addition, TNF-α and IL-6 may regulate bone metabolism indirectly by regulating adiponectin and leptin released from adipocytes.

CONCLUSION:

In this review, we first summarize the role of TNF-α and IL-6 in lipid and bone metabolisms. We further discuss how TNF-α and IL-6 regulate the communication between fat and bone, and their pathological roles in obesity-related bone disorders. Lastly, we discuss the possibility of using pro-inflammatory signaling pathway as a therapeutic target to develop drug for obesity-related bone disorders.

KEYWORDS:

IL-6; TNF-α; bone metabolism; lipid metabolism; obesity; osteoporosis

[Indexed for MEDLINE]

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